The effects of IGF-1 and erythropoietin on apoptosis and telomerase activity in necrotizing enterocolitis model
The effects of IGF-1 and erythropoietin on apoptosis and telomerase activity in necrotizing enterocolitis model
复制标题
DOI：
10.1038/s41390-020-01195-7
复制
发表时间：
2020-10-23
影响因子：
3.6
通讯作者：
Kultursay, Nilgun
中科院分区：
文献类型：
--
作者：
Akisu, Mete;Durmaz, Burak;Kultursay, Nilgun
背景缺氧/复氧（H/R）后细胞凋亡在坏死性小肠结肠炎（NEC）的发病机制中起重要作用。端粒酶活性，显示再生能力，也可能是重要的恢复过程。因此，我们的目的是研究胰岛素样生长因子-1（IGF-1）和促红细胞生成素（EPO）对H/R模型中细胞凋亡和端粒酶活性的影响。方法将幼年小鼠分为4组，每组10只Balb/c小鼠。第1组（H/R）暴露于H/R，第2组和第3组在H/R前分别用IGF-1和EPO预处理7 d。第4组为对照组。通过组织学评分评估肠损伤，并通过末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）试验评估细胞凋亡。实时荧光定量PCR检测促凋亡和抗凋亡基因表达及端粒酶活性。结果经IGF-1和EPO处理的动物组织损伤和凋亡减少，TUNEL检测和caspase活性证实。在这些动物中，除了抗凋亡基因的表达增加外，端粒酶活性也增加。然而，促凋亡基因的表达没有统计学差异。结论IGF-1和EPO对H/R损伤的保护作用可能是通过增加抗凋亡基因的表达和端粒酶活性，尤其是IGF-1的表达。这是一项全面的研究，测量各种变量，即IGF-1，EPO，细胞凋亡，凋亡和抗凋亡基因，以及NEC模型中的端粒酶活性。IGF-1和EPO可能通过增加抗凋亡基因的表达和端粒酶活性而对H/R损伤的肠道保护作用。据我们所知，以前尚未在NEC模型中研究过端粒酶活性。关于我们的研究结果，新的策略可能会实施早期明确诊断，强大的预防措施，有效的治疗方式NEC。
Background Apoptosis that occurs after hypoxia/reoxygenation (H/R) has an important role in the pathogenesis of necrotizing enterocolitis (NEC). Telomerase activity, showing the regeneration capacity, may also be important in the recovery process. Therefore, we aimed to investigate the effects of insulin-like growth factor-1 (IGF-1) and erythropoietin (EPO) on apoptosis and telomerase activity in an H/R model. Methods Young mice were divided into four groups each containing ten Balb/c mice. Group 1 (H/R) were exposed to H/R; group 2 and group 3 were pretreated with IGF-1 and EPO, respectively, for 7 days before H/R. Group 4 served as control. Intestinal injury was evaluated by histological scoring and assessment of apoptosis was performed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) test. Proapoptotic and antiapoptotic gene expressions and telomerase activity were analyzed by real-time PCR. Results IGF-1- and EPO-treated animals had decreased histological damage and apoptosis, confirmed by TUNEL test and caspase activity. Telomerase activity was increased in these animals in addition to increased expression of antiapoptotic genes. However, proapoptotic gene expressions were not statistically different. Conclusions The protective effects of IGF-1 and EPO in H/R damage may be through increased expression of antiapoptotic genes and increased telomerase activity, especially for IGF-1. Impact This is a comprehensive study measuring various variables, namely IGF-1, EPO, apoptosis, apoptotic and antiapoptotic genes, and telomerase activity in the NEC model. The intestinal protective effects of IGF-1 and EPO in H/R damage may occur through increased expression of antiapoptotic genes and increased telomerase activity. To the best of our knowledge, telomerase activity has not been investigated in the NEC model before. Regarding our results, novel strategies may be implemented for the early definitive diagnosis, robust preventive measures, and effective treatment modalities for NEC.